A Mechanistic Study of the Horner-Wadsworth-Emmons Reaction by ab initio Calculations

用从头算方法研究了Horner-Wadsworth-Emmons(HWE)反应的机理。研究表明，乙醛与三甲基膦酸锂的HWE反应发生在烯酸锂与乙醛的加成(TS1)，然后是环氧杂环烷(TS2)的生成、假酸化、P-C键断裂，然后是O-C键断裂。环氧杂环己烷的形成(TS2)是在气相和存在一个或两个二甲醚分子的情况下决定反应速度的步骤。在TS2中，生成反式烯烃的过渡态比生成顺式烯烃的过渡态更稳定。这些计算重现了产品的选择性。此外，还研究了二苯基膦乙酸甲酯衍生的锂与乙醛在乙醚分子存在下的反应。虽然该反应发生相似，但在自洽反应场(SCRF)方法中，决定反应速度的步骤是醛的加成(TS1)。在TS1中，生成顺式烯烃的过渡态比生成反式烯烃的过渡态更稳定。这些计算表明，反式烯烃可以在较高温度下在非极性溶剂中生成，而顺式烯烃则可以在较低温度下在极性溶剂中生成顺式烯烃。

The mechanism of the Horner-Wadsworth-Emmons (HWE) reaction has been investigated using ab initio calculations. This study revealed that the HWE reaction of the lithium enolate derived from trimethyl phosphonoacetate with acetaldehyde occurs with the addition of the lithium enolate to aldehyde (TS1), followed by oxaphosphetane formation (TS2), pseudoratation, P-C bond cleavage, and then O-C bond cleavage. The oxaphosphetane formation (TS2) is the rate-determining step both in the gas phase and in the presence of one or two dimethyl ether molecules. In TS2, the transition state leading to trans-olefin is more stable than the transition state leading to cis-olefin. Product selectivity is reproduced by these calculations. Also the reaction of the lithium enolate derived from methyl diphenylphosphonoacetate with acetaldehyde was studied in the presence of one diemthyl ether molecule. Although this reaction occurs similary, the rate-determining step is the addition to aldehyde (TS1) in a Self-Consistent Reaction Field (SCRF) method. In TS1, the transition state leading to cis-olefin is more stable than the transition state leading to trans-olefin. These calculations show that trans-olefins can be made in a non-polar solvent at a higher temperature, on the other hand, cis-olefins can be made by using methyl diphenylphosphonoacetate in a polar solvent at a low temperature.